Accurate quantification of kidney function with non-sedated motion-compensated pediatric MRI

项目总结： 肾盂输尿管连接部梗阻(UPJO)是一种尿流障碍，从肾盆流向近端。 输尿管，是新生儿肾积水的最常见原因。这种疾病在多达7%的人中被检测到 所有的母体超声扫描，估计有10%的新生儿有肾积水，如果留下来 如果不进行治疗，可能会导致这些患者早期肾功能发育衰竭。当前的方法 然而，评估新生儿和儿童的肾功能并不是最理想的。虽然当前引用 标准的核磁共振成像(MAG3)提供了一些有用的诊断信息；它具有侵入性，速度慢，可提供 分辨率低，不提供解剖细节，并提供潜在有害的电离辐射。因此，有 迫切需要开发一种非侵入性、安全、 准确、可重复、无辐射。因此，这项为期两年的探索性研究的主要目标是， 有两个方面：第一，开发先进的运动补偿、高时空分辨率的方法 磁共振成像(MRI)用于改进的肾小球滤过率(GFR)的量化，以及 肾功能的重要标志；第二，证明这种方法的优越性。 核重描记参照标准(MAG3)。我们响应PAR-18-743的应用程序特别是 旨在开发和评估运动健壮性、高时空分辨率动态对比度增强 用于量化GFR的MRI(DCE-MRI)(MR-GFR)以及创建新的自动化分析软件以实现 消除镇静需要的新生儿不同肾功能的稳健和可重复性评估 在年龄较大的孩子中也是如此。我们的方法将克服当前DCE-MRI技术的技术挑战 提供高时间分辨率以捕获准确所需的快速动脉输入功能动态 计算GFR，补偿不可避免的呼吸和大体运动以重建高质量 并将提供可靠、快速、自动化的后处理技术，以实现准确的GFR计算。AS 一种非侵入性、运动稳健、无辐射的成像技术，可以在更高的位置描绘肾脏结构 随着分辨率的提高，MR-GFR将首次提供MAG3无法提供的诊断信息。 了解UPJO的范围和严重程度(以及由此导致的肾积水)至关重要 不能轻描淡写；因为在缺乏这一信息的情况下，儿童将受益于立即 手术在接受治疗时可能会被忽视或推迟；而那些可能从更多的 保守的方法(即观望等待)可能会接受不必要的手术干预。事实上，这一点 新的成像方法有望显著改善临床决策。成功者 完成我们的目标将使1)准确评估肾功能；2)预测 功能衰退；3)确定是否需要手术。DCE-MRI有望迅速 一旦引入临床实践，对几种影响肾功能的疾病的翻译影响。

Project Summary: Ureteropelvic junction obstruction (UPJO) is an impairment of urine flow from the renal pelvis into the proximal ureter and is the most common cause of hydronephrosis in neonates. This disorder is detected in up to 7% of all maternal ultrasound scans, and an estimated 10% of these newborns have hydronephrosis, which, if left untreated, may result in early failure of functional renal development in these patients. Current methods of assessing kidney function in neonates and children are less than optimal, however. While the current reference standard, nuclear renography (MAG3), yields some useful diagnostic information; it is invasive, slow, provides low resolution, does not offer anatomic detail, and delivers potentially harmful ionizing radiation. Thus, there is an urgent, unmet need to develop a method for functional imaging of kidneys that is non-invasive, safe, accurate, reproducible and radiation-free. The primary objective of this exploratory, two-year study, therefore, is two-fold: first, to develop advanced methods of motion-compensated, high spatial and temporal resolution magnetic resonance imaging (MRI) for the improved quantification of the glomerular filtration rate (GFR), an important marker of renal function; and second, to demonstrate the superiority of this method over the current reference standard, nuclear renography (MAG3). Our application in response to PAR-18-743 is specifically aimed at developing, and evaluating motion-robust, high spatiotemporal resolution dynamic contrast-enhanced MRI (DCE-MRI) for quantifying GFR (MR-GFR) as well as creating new automated analysis software to enable the robust and reproducible assessment of differential renal function in newborns eliminating need for sedation, and in older children. Our method will overcome the technical challenges of current DCE-MRI techniques providing high temporal resolution to capture fast arterial input function dynamics required for accurate computation of GFR, compensate for unavoidable respiratory and bulk motion to reconstruct high quality images and will provide robust, fast, automated post processing techniques for accurate GFR computation. As a non-invasive, motion-robust, radiation-free imaging technique that can depict renal structures at much higher resolution, MR-GFR will offer, for the first time, a level of diagnostic information that is unattainable with MAG3. The critical importance of understanding the extent and severity of UPJO (and resulting hydronephrosis) cannot be understated; for in the absence of this information, children who stand to benefit from immediate surgery might be overlooked or delayed in receiving treatment; and those who might benefit from a more conservative approach (i.e., watching waiting) might receive an unnecessary surgical intervention. Indeed, this novel imaging approach is expected to substantially improve clinical decision-making. The successful completion of our aims will enable 1) assessment of renal function accurately; 2) predicting the likelihood of functional decline; and 3) determining whether surgery is indicated. DCE-MRI is expected to have rapid translational impact for several diseases effecting kidney function once it is introduced into clinical practice.